Histone deacetylase-1 represses transcription by interacting with zinc-fingers and interfering with the DNA binding activity of Sp1.
Sp1 activates the transcription of many cellular and viral genes, and histone deacetylase 1 (HDAC1) removes the acetyl group of nucleosomal core histones. Treatment of cells with the histone deacetylase 1 inhibitor, TSA, robustly activates the transcription of the Sp1-dependent promoters, suggesting the inhibition of Sp1 activity which is critical ... in the activation of transcription, by HDAC1. We assessed the protein-protein interactions occurring between Sp1 and HDAC1, and the transcriptional regulatory mechanism controlled by this interaction. In vitro GST fusion pull down assays, co-immunoprecipitation, and mammalian two-hybrid assays revealed that the HDAC1 noncatalytic domain (a.a. 237-482) interacts directly with the zinc-finger DNA binding domain of Sp1. DNase I footprinting revealed that this interaction prevents the binding of Sp1 zinc-fingers to the target GC-box. Gal4-HDAC1 fusion, targeted proximally to the GC-boxes, potently repressed the transcription of pG5-5x(GC)-Luc, in which Sp1 potently activates transcription. This repression of transcription does not involve the deacetylase activity of HDAC1, and is accomplished by the direct protein-protein interactions which occur between the Sp1 zinc-finger DNA binding domain and HDAC1, which interferes with the promoter GC-box binding of Sp1.
Mesh Terms:
Animals, Base Sequence, Binding Sites, Cell Line, Cercopithecus aethiops, DNA, Enzyme Inhibitors, Histone Deacetylase Inhibitors, Histone Deacetylases, Hydroxamic Acids, Recombinant Proteins, Sp1 Transcription Factor, Transcription, Genetic, Two-Hybrid System Techniques, Zinc Fingers
Animals, Base Sequence, Binding Sites, Cell Line, Cercopithecus aethiops, DNA, Enzyme Inhibitors, Histone Deacetylase Inhibitors, Histone Deacetylases, Hydroxamic Acids, Recombinant Proteins, Sp1 Transcription Factor, Transcription, Genetic, Two-Hybrid System Techniques, Zinc Fingers
Cell. Physiol. Biochem.
Date: Aug. 27, 2005
PubMed ID: 16121030
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